The specific aim of this research proposal is an understanding of the roles of the various avian retrovirus genomic regions in viral replication and transformation. This will be accomplished by biochemical analyses of nonconditional mutants of Rous sarcoma virus. These include mutants in env and pol as well as in a mutant lacking sequences necessary for genomic RNA packaging. These mutants will also be utilized in order to investigate recombination between host and viral sequences and the generation of new transforming viruses. These studies will be important in understanding the generation of transforming sequences from normal cellular genes. In addition, we are commencing work on the isolation of mutants of acute leukemia viruses which transform myeloid lineage cells. The target cell specificity of the transforming sequences of these viruses will be explored. These studies will aid in development of a model of evolution of and oncogenesis by retroviruses with different transforming sequences.